Enzymatic colorimetric analysis of metabolites provides signatures of energy conversion and biosynthesis associated with disease onsets and progressions. Miniaturized photodetectors based on emerging ...two-dimensional transition metal dichalcogenides (TMDCs) promise to advance point-of-care diagnosis employing highly sensitive enzymatic colorimetric detection. Reducing diagnosis costs requires a batched multisample assay. The construction of few-layer TMDC photodetector arrays with consistent performance is imperative to realize optical signal detection for a miniature batched multisample enzymatic colorimetric assay. However, few studies have promoted an optical reader with TMDC photodetector arrays for on-chip operation. Here, we constructed 4 × 4 pixel arrays of miniaturized molybdenum disulfide (MoS2) photodetectors and integrated them with microfluidic enzyme reaction chambers to create an optoelectronic biosensor chip device. The fabricated device allowed us to achieve arrayed on-chip enzymatic colorimetric detection of d-lactate, a blood biomarker signifying the bacterial translocation from the intestine, with a limit of detection that is 1000-fold smaller than the clinical baseline, a 10 min assay time, high selectivity, and reasonably small variability across the entire arrays. The enzyme (Ez)/MoS2 optoelectronic biosensor unit consistently detected d-lactate in clinically important biofluids, such as saliva, urine, plasma, and serum of swine and humans with a wide detection range (10–3–103 μg/mL). Furthermore, the biosensor enabled us to show that high serum d-lactate levels are associated with the symptoms of systemic infection and inflammation. The lensless, optical waveguide-free device architecture should readily facilitate development of a monolithically integrated hand-held module for timely, cost-effective diagnosis of metabolic disorders in near-patient settings.
Laser-induced graphene (LIG) has been extensively researched due to its facile fabrication on various carbon-containing substrates using simple laser scribing. In recent years, advancements have ...enabled the production of LIG on environmentally friendly substrates, opening new possibilities for designing sustainable electronics that minimize adverse environmental effects. This paper provides an overview of the latest advancements in manufacturing technologies for LIG on eco-friendly substrates, such as paper, wood, lignin biomass, cloth, food, and biocompatible parylene-C. Furthermore, a comparative analysis is conducted between LIG generated on eco-friendly substrates and graphene patterns printed using commercially available graphene ink. This analysis emphasizes the potential efficacy of LIG as an efficient manufacturing technique for producing conductive graphene patterns. The review also outlines the remaining challenges requiring attention to advance these manufacturing processes and outlooks future opportunities, which can serve as a valuable guide for both novice researchers unfamiliar with LIG and experienced researchers aiming to utilize eco-friendly substrates in their study.
The superior electronic and mechanical properties of two-dimensional layered transition-metal dichalcogenides could be exploited to make a broad range of devices with attractive functionalities. ...However, the nanofabrication of such layered material-based devices still needs resist-based lithography and plasma etching processes for patterning layered materials into functional device features. Such patterning processes lead to unavoidable contaminations, to which the transport characteristics of atomically thin-layered materials are very sensitive. More seriously, such lithography-introduced contaminants cannot be safely eliminated by conventional semiconductor cleaning approaches. This challenge seriously retards the manufacturing of large arrays of layered material-based devices with consistent characteristics. Toward addressing this challenge, we introduce a rubbing-induced site-selective growth method capable of directly generating few-layer MoS2 device patterns without the need of any additional patterning processes. This method consists of two critical steps: (i) a damage-free mechanical rubbing process for generating microscale triboelectric charge patterns on a dielectric surface and (ii) site-selective deposition of MoS2 within rubbing-induced charge patterns. Our microscopy characterizations in combination with finite element analysis indicate that the field magnitude distribution within triboelectric charge patterns determines the morphologies of grown MoS2 patterns. In addition, the MoS2 line patterns produced by the presented method have been implemented for making arrays of working transistors and memristors. These devices exhibit a high yield and good uniformity in their electronic properties over large areas. The presented method could be further developed into a cost-efficient nanomanufacturing approach for producing functional device patterns based on various layered materials.
The superior electronic and mechanical properties of two-dimensional layered transition-metal dichalcogenides could be exploited to make a broad range of devices with attractive functionalities. ...However, the nanofabrication of such layered material-based devices still needs resist-based lithography and plasma etching processes for patterning layered materials into functional device features. Such patterning processes lead to unavoidable contaminations, to which the transport characteristics of atomically thin-layered materials are very sensitive. More seriously, such lithography-introduced contaminants cannot be safely eliminated by conventional semiconductor cleaning approaches. This challenge seriously retards the manufacturing of large arrays of layered material-based devices with consistent characteristics. Toward addressing this challenge, we introduce a rubbing-induced site-selective growth method capable of directly generating few-layer MoS
device patterns without the need of any additional patterning processes. This method consists of two critical steps: (i) a damage-free mechanical rubbing process for generating microscale triboelectric charge patterns on a dielectric surface and (ii) site-selective deposition of MoS
within rubbing-induced charge patterns. Our microscopy characterizations in combination with finite element analysis indicate that the field magnitude distribution within triboelectric charge patterns determines the morphologies of grown MoS
patterns. In addition, the MoS
line patterns produced by the presented method have been implemented for making arrays of working transistors and memristors. These devices exhibit a high yield and good uniformity in their electronic properties over large areas. The presented method could be further developed into a cost-efficient nanomanufacturing approach for producing functional device patterns based on various layered materials.
Bacterial infections leading to sepsis are a major cause of deaths in the intensive care unit. Unfortunately, no effective methods are available to capture the early onset of infectious sepsis near ...the patient with both speed and sensitivity required for timely clinical treatment. To fill the gap, the authors develop a highly miniaturized (2.5 × 2.5 µm2) plasmo‐photoelectronic nanostructure device that detected citrullinated histone H3 (CitH3), a biomarker released to the blood circulatory system by neutrophils. Rapidly detecting CitH3 with high sensitivity has the great potential to prevent infections from developing life‐threatening septic shock. To this end, the author's device incorporates structurally engineered arrayed hemispherical gold nanoparticles that are functionalized with high‐affinity antibodies. A nanoplasmonic resonance shift induces a photoconduction increase in a few‐layer molybdenum disulfide (MoS2) channel, and it provides the sensor signal. The device achieves label‐free detection of serum CitH3 with a 5‐log dynamic range from 10−4 to 101 ng mL and a sample‐to‐answer time <20 min. Using this biosensor, the authors longitudinally measure the dynamic CitH3 profiles of individual living mice in a sepsis model at high resolution over 12 hours. The developed biosensor may be poised for future translation to personalized management of systemic bacterial infections.
The lack of an appropriate biosensing technology to detect the early onset of bacterial infections has prohibited timely clinical treatment of sepitc shock. This article presents a highly miniaturized plasmo‐photoelectronic device incorporating high‐affinity antibody‐conjugated hemispherical gold nanoparticles and a few‐layer molybdenum disulfide (MoS2) photoconductive channel to detect a blood biomarker released by neutrophils with high speed and sensitivity.
Rapid diagnosis of coronavirus disease 2019 (COVID-19) is key for the long-term control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) amid renewed threats of mutated SARS-CoV-2 ...around the world. Here, we report on an electrical label-free detection of SARS-CoV-2 in nasopharyngeal swab samples directly collected from outpatients or in saliva-relevant conditions by using a remote floating-gate field-effect transistor (RFGFET) with a 2-dimensional reduced graphene oxide (rGO) sensing membrane. RFGFET sensors demonstrate rapid detection (<5 min), a 90.6% accuracy from 8 nasal swab samples measured by 4 different devices for each sample, and a coefficient of variation (CV) < 6%. Also, RFGFET sensors display a limit of detection (LOD) of pseudo-SARS-CoV-2 that is 10 000-fold lower than enzyme-linked immunosorbent assays, with a comparable LOD to that of reverse transcription-polymerase chain reaction (RT-PCR) for patient samples. To achieve this, comprehensive systematic studies were performed regarding interactions between SARS-CoV-2 and spike proteins, neutralizing antibodies, and angiotensin-converting enzyme 2, as either a biomarker (detection target) or a sensing probe (receptor) functionalized on the rGO sensing membrane. Taken together, this work may have an immense effect on positioning FET bioelectronics for rapid SARS-CoV-2 diagnostics.
Despite intensive research of nanomaterials-based field-effect transistors (FETs) as a rapid diagnostic tool, it remains to be seen for FET sensors to be used for clinical applications due to a lack ...of stability, reliability, reproducibility, and scalability for mass production. Herein, we propose a remote floating-gate (RFG) FET configuration to eliminate device-to-device variations of two-dimensional reduced graphene oxide (rGO) sensing surfaces and most of the instability at the solution interface. Also, critical mechanistic factors behind the electrochemical instability of rGO such as severe drift and hysteresis were identified through extensive studies on rGO–solution interfaces varied by rGO thickness, coverage, and reduction temperature. rGO surfaces in our RFGFET structure displayed a Nernstian response of 54 mV/pH (from pH 2 to 11) with a 90% yield (9 samples out of total 10), coefficient of variation (CV) < 3%, and a low drift rate of 2%, all of which were calculated from the absolute measurement values. As proof-of-concept, we demonstrated highly reliable, reproducible, and label-free detection of spike proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a saliva-relevant media with concentrations ranging from 500 fg/mL to 5 μg/mL, with an R 2 value of 0.984 and CV < 3%, and a guaranteed limit of detection at a few pg/mL. Taken together, this new platform may have an immense effect on positioning FET bioelectronics in a clinical setting for detecting SARS-CoV-2.
Among other layered two-dimensional (2D) materials, transition metal dichalcogenides (TMDCs) have revealed their importance in developing novel electronic devices such as field-effect transistors ...(FETs), optoelectronics, and biomedical sensors. The superior electrical, mechanical, and optoelectronic characteristics, in combination with naturally formed sizable and tunable bandgap of TMDCs, have turned out to be promising for making new biomedical sensors. Despite such a bright prospect, there remain critical scientific and technical gaps that should be filled to enable advanced and practical biomedical sensor applications. Specifically, such gaps include (i) loss of operation stability of MoS2 FET biosensors under wet conditions, (ii) lack of reusability of the electronic biosensors made of TMDCs, and (iii) absence of scalable nanofabrication methods capable of producing well-defined TMDC device patterns.A series of studies presented in this thesis leveraged scientific and technical knowledge to deal with the aforementioned urgent demands and was categorized into three main topics: (i) devise a cycle-wise method for operating MoS2 FET biosensors integrated with a microfluidic channel, which alleviates the liquid-solution-induced issues; (ii) design a new biosensor structure consisting of a bio-tunable nanoplasmonic window and a low-noise few-layer MoS2 photodetector, which can enable highly sensitive, fast, and reusable biosensing processes; (iii) invent scalable nanofabrication and nanomanufacturing approaches capable of producing orderly-arranged TMDCs device channel patterns at designated locations on a target substrate.The first topic (i.e., the second chapter) presents a cycle-wise method for operating MoS2 FET biosensors to quantify fM-level disease-related biomarkers. This approach enhances the detection performance of the MoS2 FET sensors by providing a series of advantages such as fast detection, low-noise, and high specificity. In this detection scheme, the MoS2 FET sensing channel is integrated with a microfluidic structure that delivers reagent fluids to the sensor in a time-sequence order. The reagent fluids (e.g., Analyte solution, Deionized (DI) water, Phosphate buffer solution (PBS), and Air) periodically set the sensing channel into four different cycle stages: incubation, flushing, drying, and measurement (i.e., an IFMD cycle). Such a cycle-wise approach can physically prevent the electrical sensing components from being exposed to liquid solutions, which significantly mitigates liquid-solution-induced issues such as electrochemical damage, electronic noise, signal screening, and nonspecific adsorption. Due to such benefits, the cycle-wise method can significantly improve sensors’ sensitivity, durability, detection limit, and specificity. In my experimental demonstration, MoS2 FET sensors, in combination with the cycle-wise method, can quantify streptavidin and interleukin -1β (IL-1β) biomarkers with a detection limit as low as 1 fM within a total assay time less than 23 min.The second part (i.e., the third and fourth chapters) exhibits a highly sensitive and label-free biosensor consisting of a plasmonic window that is bearing gold nanoparticles (AuNPs) and a few-layer MoS2 photodetector. The plasmonic window is located 100 µm above the MoS2 photodetector, which physically separates the MoS2 device from the plasmonic window where the binding reaction happens. Due to such a new decoupled sensor structure, the few-layer MoS2 photodetector can be reused for multiple sensing cycles. With presence of an analyte solution to the plasmonic window, binding reactions occur at the surface of antibody-functionalized AuNPs, which results in the redshift of the extinction spectrum peak of the AuNPs due to the shift of localized surface plasmon resonance (LSPR) peak. In this process, the extinction peak shift, dependent on the concentration of analyte solution, dynamically modulates the intensity of the light transmitting to the MoS2 photodetector. The measured photocurrents here serve as the sensor response signals for quantifying the concentration of analyte solutions. Such a new biosensor can quantify the concentrations of interleukin-1β (IL-1β) with limit-of-detection (LOD) of 250 fg/mL (14 fM) and dynamic concentration range as large as 106 . The assay time for quantifying each concentration requires ~ 10 min. Multiple such biosensors have been also utilized to detect CitH3, a biomarker indicating the sepsis. Due to the excellent detection capabilities such as high sensitivity, high accuracy, high detection speed, and label-free detection, the developed biosensors can successfully quantify the concentrations of circulating CitH3 and other biomarkers such as procalcitonin (PCT) and IL-1β in a living mouse.The third part (i.e., the fifth and sixth chapter) focuses on developing scalable nanofabrication methods capable of producing layered semiconductors (TMDCs, e.g., MoS2) patterns without requiring additional resist-based lithography and plasma-based etching processes. Specifically, various techniques (e.g., triboelectric effect or inkjet printing) have been applied to modify the surface property of a substrate, which results in triboelectric charge patterns or local topography changes on the substrate. In the basis of these two surface modification approaches, new nanofabrication methods are named as rubbing-induced site-selective (RISS) and inkjet-defined site-selective (IDSS), respectively. The modified regions of the substrate possess a high affinity to precursor molecules, thus inducing site-selective nucleation of MoS2 during chemical vapor deposition (CVD). The site-selectively formed MoS2 lines and pixels by RISS and IDSS have been utilized to produce arrays of field-effect transistors (FETs). The yield of working FETs produced by RISS is about ~ 76 %, and such devices exhibit a good device-to-device consistency in transport characteristics. The site-selective synthesis methods presented here are facile, scalable, and cost-efficient. More importantly, they do not require exquisite lithographic tools and reduce the chance of serious contaminations. The presented works have engineered layered semiconductors and device structures based on the scientific knowledge and device physics to realize practical and functional TMDC-based biomedical devices. Additionally, the nanofabrication methods invented in this thesis work could be further developed into cost-efficient and scalable nanomanufacturing techniques that will speed up the development of a wide variety of new device applications made of layered semiconductors.
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